ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma

Valentina Frezza, Claudia Fierro, Elena Gatti, Angelo Peschiaroli, Anna Maria Lena, Margherita Annicchiarico Petruzzelli, Eleonora Candi, Lucia Anemona, Alessandro Mauriello, Pier Giuseppe Pelicci, Gerry Melino, Francesca Bernassola

Research output: Contribution to journalArticle

Abstract

Accumulating evidence has proved that deregulation of ΔNp63 expression plays an oncogenic role in head and neck squamous cell carcinomas (HNSCCs). Besides p63, the type 1-insulin-like growth factor (IGF) signalling pathway has been implicated in HNSCC development and progression. Most insulin/IGF1 signalling converges intracellularly onto the protein adaptor insulin receptor substrate-1 (IRS-1) that transmits signals from the receptor to downstream effectors, including the PI3K/AKT and the MAPK kinase pathways, which, ultimately, promote proliferation, invasion, and cell survival. Here we report that p63 directly controls IRS1 transcription and cellular abundance and fosters the PI3K/AKT and MAPK downstream signalling pathways. Inactivation of ΔNp63 expression indeed reduces tumour cell responsiveness to IGF1 stimulation, and inhibits the growth potential of HNSCC cells. In addition, a positive correlation was observed between p63 and IRS1 expression in human HNSCC tissue arrays and in publicly available gene expression data. Our findings indicate that aberrant expression of ΔNp63 in HNSSC may act as an oncogenic stimulus by altering the IGF signalling pathway.

Original languageEnglish
Pages (from-to)4224-4240
Number of pages17
JournalAging
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 1 2018

    Fingerprint

Keywords

  • Head and neck tumours
  • IGF system
  • IRS1
  • P53 family
  • P63

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

Cite this

Frezza, V., Fierro, C., Gatti, E., Peschiaroli, A., Lena, A. M., Petruzzelli, M. A., Candi, E., Anemona, L., Mauriello, A., Pelicci, P. G., Melino, G., & Bernassola, F. (2018). ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma. Aging, 10(12), 4224-4240. https://doi.org/10.18632/aging.101725